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CMT — Kleopas Kleopa, M.D.

Viral delivery of the connexin 32 gene allows increased protein production (arrows) in the myelin sheath. Click to enlarge image.

Charcot-Marie-Tooth Disease (CMT)

Kleopas Kleopa, professor at the Cyprus Institute of Neurology and Genetics in Nicosia, Cyprus, was awarded an MDA research grant totaling $280,945 over a period of three years to develop gene therapy in a mouse model of X-linked Charcot-Marie-Tooth disease (CMT).

CMTX is due to mutations in the gene for connexin 32. This protein forms connections between layers of the insulating material around nerve cells, called myelin. Loss of connexin prevents the nerve cell from functioning properly, leading to muscle atrophy, weakness and sensory loss in the limbs. Kleopa has generated a mouse model of the disease, and has developed virus-like particles that can carry a functional copy of the gene, increasing connexin 32 protein production when delivered directly to the nerve.

Now, Kleopa will study a combination of gene delivery methods, including direct injection into the nerves, muscles and spinal cord. He also will examine treated mice for signs that the gene improves neuropathy (nerve abnormalities).

“Transgenic mice are particularly well suited for this study because treatment of peripheral neuropathy can only be validated in a vertebrate animal model, where the pathology can be studied in peripheral nerves,” Kleopa says. “Furthermore, this particular mouse model reproduces all major pathological aspects of the human disease, and therefore it is relevant to test potential treatments.

“In the last two decades research in the field of inherited neuropathies, especially the common forms, has provided many insights into the causes and mechanisms of disease. Developing genetic treatments, using the recently generated disease models, is an important and timely approach to also provide potential therapies for these disorders in the near future.”